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1.
Prev Med Rep ; 41: 102708, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38595730

RESUMEN

Objective: To help inform decisions regarding the equitable implementation of obesity interventions, we examined whether interventions were equitably reaching the most vulnerable communities, identified communities that received fewer interventions than expected, and estimated the effect of 'dose' of interventions on obesity prevalence. Methods: We created a database to identify and characterize obesity-related interventions implemented in Los Angeles County from 2005 to 2015 linked to community-level sociodemographic and obesity prevalence data. We ran generalized linear models with a Gamma distribution and log link to determine if interventions were directed toward vulnerable communities and to identify communities that received fewer interventions than expected. We ran fixed-effects models to estimate the association between obesity prevalence and intervention strategy count among preschool-aged children enrolled in the Special Supplemental Nutrition Assistance Program for Women Infants and Children. Results: We found that interventions targeted vulnerable communities with high poverty rates and percentages of minority residents. The small cluster of communities that received fewer interventions than expected tended to have poor socioeconomic profiles. Communities which received more intervention strategies saw greater declines in obesity prevalence (ß = -0.023; 95 % CI: -0.031, -0.016). Conclusions: It is important to determine if interventions are equitably reaching vulnerable populations as resources to tackle childhood obesity become available. Evaluating the population impact of multiple interventions implemented simultaneously presents methodological challenges in measuring intervention dose and identifying cost-effective strategies. Addressing these challenges must be an important research priority as community-wide interventions involve multiple intervention strategies to reduce health disparities.

2.
Anal Chem ; 96(8): 3593-3599, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38347729

RESUMEN

Coated blade spray (CBS) is a microextraction technology with blades that serve as both the extraction device and the electrospray ionization (ESI) emitter. CBS is designed for easy and rapid extraction of analytes in complex matrices as well as ESI directly from the blade. The technology selectively enriches the components of interest on a coated metal blade. The coating consists of a selective polymer. So far, CBS has only been coupled with mass spectrometry but never with ion mobility spectrometry (IMS), where ions are separated and detected based on their ion mobility in a drift gas under the influence of an electric field, while instrumentation is compact and easy to operate so that the advantages of CBS can be particularly well exploited. Therefore, this work focuses on coupling CBS with our previously described ESI-IMS. The ion mobility spectrometer has a drift length of only 75 mm and provides a high resolving power of RP = 100. In this work, preliminary measurements of CBS-IMS are presented. In particular, the detection of benzodiazepines and ketamine in drinks and the pesticide isoproturon in water samples is shown to demonstrate the feasibility of CBS-IMS.

3.
Clin Cardiol ; 47(2): e24197, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38069663

RESUMEN

BACKGROUND: Postinterventional sonographic assessment of the femoral artery after transfemoral transcatheter aortic valve replacement (TF-TAVR) has the potential to identify several pathologies. We investigated the incidence and risk factors of femoral vessel complications in a modern TAVR collective using postinterventional sonography. METHODS: Between September 2017 and March 2022, 480 patients underwent TF-TAVR with postinterventional femoral sonography at a single center. Clinical outcomes and adverse events were analyzed after the Valve Academic Research Consortium 3 (VARC-3) criteria. RESULTS: In this cohort (51.2% male; age 80 ± 7.5 years, median EuroSCORE II 3.7) 74.8% (n = 359) were implanted with a self-expandable and 25.2% (n = 121) with a balloon-expandable valve. The main access (valve-delivery) was located right in 91.4% (n = 438), and the primary closure system was Proglide in 95% (n = 456). Vascular complications (VC) were observed in 29.16% (n = 140) of patients; 23.3% (n = 112) presented with minor- and 5.8% (n = 28) with major VC. Postinterventional femoral artery stenosis on the main access was observed in 9.8% (n = 47). Multivariable logistic regression analysis revealed female sex (p = .03, odds ratio [OR] 2.32, 95% confidence interval [CI] 1.09-4.89) and the number of used endovascular closure devices (p = .014, OR 0.11, 95%CI 0.02-0.64) as predictive factors for femoral artery stenosis. CONCLUSIONS: The incidence of postinterventional femoral artery stenosis following TF-TAVR was higher than expected with a number of used closure devices and female sex being independent risk factors. Considering the continuous advance of TAVR in low-risk patients with preserved physical activity, emphasis should be directed at the correct diagnosis and follow-up of these complications.


Asunto(s)
Estenosis de la Válvula Aórtica , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Enfermedades Vasculares , Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Prótesis Valvulares Cardíacas/efectos adversos , Constricción Patológica/complicaciones , Constricción Patológica/cirugía , Resultado del Tratamiento , Factores de Riesgo , Arteria Femoral/diagnóstico por imagen , Arteria Femoral/cirugía , Estenosis de la Válvula Aórtica/diagnóstico , Estudios Retrospectivos
5.
Am J Mens Health ; 17(5): 15579883231197910, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37771162

RESUMEN

The impact of ejaculatory abstinence on semen parameters using in-office semen analyses has been well-established; however, their variability has not been evaluated in men using mail-in semen analysis kits. Our study aims to describe how the sperm parameters using mail-in semen analysis tests change with abstinence and validate their equivalence to those seen with in-office semen analysis tests. We retrospectively reviewed the semen analysis results of men using mail-in semen analysis tests provided by Give Legacy, Inc (Legacy) facilities from 2019 to 2021. We collected their demographic information, abstinence duration, and semen parameters (conventional and kinematic) from their records. Semen samples were categorized as normozoospermic and oligozoospermic based on concentration. The shape of the relationship between abstinence duration and semen parameters was assessed via generalized additive models. We have collected 3,469 unique samples provided by 2,609 (75%) normozoospermic men and 860 (25%) oligozoospermic from all over the United States. In normozoospermic men, longer periods of sexual abstinence were linked to higher levels of sperm concentration, total sperm count, and total motile sperm. However, there was a decline in both total and progressive motility. Conversely, in oligozoospermic men, extended periods of abstinence led to a rapid decline in total motile sperm, as well as total and progressive motility. There was no significant correlation observed between sexual abstinence and variations in sperm morphology. Our study shows that variability of sperm parameters with abstinence, as measured through mail-in semen analysis tests, is comparable to the patterns observed with conventional in-office sperm testing.


Asunto(s)
Semen , Abstinencia Sexual , Masculino , Humanos , Estudios Retrospectivos , Servicios Postales , Motilidad Espermática , Análisis de Semen , Espermatozoides
6.
Mar Drugs ; 21(9)2023 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-37755073

RESUMEN

Marine sponges of the subclass Keratosa originated on our planet about 900 million years ago and represent evolutionarily ancient and hierarchically structured biological materials. One of them, proteinaceous spongin, is responsible for the formation of 3D structured fibrous skeletons and remains enigmatic with complex chemistry. The objective of this study was to investigate the interaction of spongin with iron ions in a marine environment due to biocorrosion, leading to the occurrence of lepidocrocite. For this purpose, a biomimetic approach for the development of a new lepidocrocite-containing 3D spongin scaffold under laboratory conditions at 24 °C using artificial seawater and iron is described for the first time. This method helps to obtain a new composite as "Iron-Spongin", which was characterized by infrared spectroscopy and thermogravimetry. Furthermore, sophisticated techniques such as X-ray fluorescence, microscope technique, and X-Ray diffraction were used to determine the structure. This research proposed a corresponding mechanism of lepidocrocite formation, which may be connected with the spongin amino acids functional groups. Moreover, the potential application of the biocomposite as an electrochemical dopamine sensor is proposed. The conducted research not only shows the mechanism or sensor properties of "Iron-spongin" but also opens the door to other applications of these multifunctional materials.


Asunto(s)
Hierro , Poríferos , Animales , Biomimética , Dopamina
7.
Ethics Hum Res ; 45(3): 18-28, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37167474

RESUMEN

This paper argues that offering entry into a lottery as an incentive to those who participate in research studies represents a challenge to the principle of informed, coercion-free consent that is considered an essential ingredient of permissible recruitment to studies. This is, first, because information about the chances of winning in this context is normally unavailable to potential participants and, without this, they cannot accurately weigh up the risks and potential benefits of participation. Second, even when this information is available, such an incentive capitalizes, I contend, on the difficulty of weighing up small probabilities, exploiting the fact that people tend to be beset by cognitive biases that make it challenging to make decisions rationally. The resulting conclusion is that we should not view lotteries as more ethical than simply paying participants, when the latter is feasible.


Asunto(s)
Consentimiento Informado , Motivación , Humanos
9.
World J Mens Health ; 41(4): 920-927, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36792088

RESUMEN

PURPOSE: To evaluate the relationship between regional geography and sperm parameters in a cohort of American men using at-home mail-in semen collection kits with no previous self-reported history of male factor infertility. MATERIALS AND METHODS: In this study, 5,822 men from six different regions of the United States (Northeast, Southeast, Midwest, West, Pacific, and Southwest) who self-requested semen analysis between 2019 and 2021 were enrolled. RESULTS: Across the entire cohort, the mean sperm concentration was 43.79±55.43 ×106 sperm/mL; total sperm count 138.93±149.96 ×106 sperm/mL; total motile sperm 54.73±81.90 ×106/ejaculate; total motility 30.18%±22.87%; progressive motility 21.61%±17.32%; sperm with normal morphology 8.79%±8.87%. Patients from the West region displayed lower median sperm concentration, total motile sperm, and total motility than men from the other four regional areas. A lower median total sperm count, and lower median progressive motility were also detected among patients in the Southwest region. Conversely, higher results were detected in patients from the Midwest (higher median total motile sperm, total and motility) and from the Northeast (higher median sperm concentration and total sperm count) regions. Men from the Southeast (OR, 1.3168; 95% CI, 1.1142-1.5563) and Southwest (OR, 1.3145; 95% CI, 1.0735-1.6096) regions were more likely to have oligozoospermia than those living elsewhere. CONCLUSIONS: This study provides the most comprehensive and up-to-date report on semen parameter variability among a cohort of men living in six different regions of the continental USA. This study will pave the way into a deeper discussion of the interplay between geography, social determinants of fertility care and semen quality.

10.
Microbiol Spectr ; 11(1): e0370922, 2023 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-36688648

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binding antibody (Ab) levels following vaccination or natural infection could be used as a surrogate for immune protection if results of serological assays were standardized to yield quantitative results using an international standard. Using a bead-based serological assay (Luminex xMAP), anti-receptor binding domain (anti-RBD) Ab levels were determined for 1,450 participants enrolled in the Los Angeles Pandemic Surveillance Cohort (LAPSC) study. For 123 participants, SARS-CoV-2 binding antibody unit (BAU) levels were also quantified using WHO standards and then compared to the semiquantitative results. Samples were chosen to represent the range of results and time from vaccination. Antibody levels and decay rates were then compared using unadjusted and adjusted linear regression models. The linear range of the assay used in this study was determined to be 300 to 5,000 mean fluorescence intensity units (MFI). Among the fully vaccinated groups (vaccinated only and vaccinated with past infection), 84.8% had anti-RBD MFI values above the linear range of >5,000 MFI, and 33.8% had values of >15,000 MFI. Among vaccinated participants with past infection (hybrid immunity), 97% had anti-RBD values of >5,000 MFI and 70% (120/171) had anti-RBD values of >15,000 MFI. In the subgroup quantified using the WHO control, BAU levels were significantly higher than the semiquantitative MFI results. In vaccinated participants, Ab decay levels were similar between infected and noninfected groups (P = 0.337). These results demonstrate that accurate quantitation is possible if standardized with an international standard. BAU can then be compared over time or between subjects and would be useful in clinical decision making. IMPORTANCE Accurate quantification of SARS-CoV-2-specific antibodies can be achieved using a universal standard with sample dilution within the linear range. With hybrid immunity being now common, it is critical to use protocols adapted to high Ab levels to standardize serological results. We validated this approach with the Los Angeles Pandemic Surveillance Cohort by comparing the antibody decay rates in vaccinated participants and vaccinated infected participants.


Asunto(s)
COVID-19 , Vacunas , Humanos , SARS-CoV-2 , COVID-19/prevención & control , Anticuerpos Antivirales , Vacunación , Organización Mundial de la Salud
11.
Health Promot Pract ; 24(3): 560-565, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-35043717

RESUMEN

Despite major public health investments over the past several decades, little progress has been made in reducing the prevalence of obesity among school-aged children in the United States. In 2007, the Redondo Beach Unified School District (RBUSD) and the Beach Cities Health District launched a wellness initiative, LiveWell Kids, that included multi-level interventions to improve nutrition and increase physical activity. The initiative also included annual measurements of height and weight among all kindergartners and first, third, and fifth graders in the eight elementary schools in the RBUSD. To assess trends in obesity prevalence, we analyzed height and weight data collected during the 2008 to 2009 to 2018 to 2019 school years. To more fully assess the impact of the initiative, we conducted a least-squares regression difference-in-differences analysis of data from the California Physical Fitness Testing Program on measured height and weight among fifth graders from the RBUSD, three neighboring school districts, and Los Angeles County overall. Among elementary school students in the RBUSD, obesity prevalence decreased from 13.9% in 2008 to 2009 to 6.4% in 2018 to 2019. Significant declines in prevalence were observed in all eight elementary schools, and across all grade levels and demographic groups. Among fifth graders, a similar decline in obesity prevalence was not observed in the other school districts or the county overall. The findings suggest that interventions that adhere to the socio-ecologic model and engage students, parents, and school personnel at all levels while also addressing school and community environments may reduce obesity prevalence among elementary school-aged children.


Asunto(s)
Obesidad Infantil , Niño , Humanos , Estados Unidos/epidemiología , Obesidad Infantil/epidemiología , Obesidad Infantil/prevención & control , Instituciones Académicas , Ejercicio Físico , Salud Pública , Estudiantes , Promoción de la Salud
12.
Ann Thorac Surg ; 115(3): 656-662, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-35779601

RESUMEN

BACKGROUND: Valve repair is the procedure of choice for congenital aortic valve disease. With increasing experience, the surgical armamentarium broadened from simple commissurotomy to more complex techniques. We report our 30-year experience with pediatric aortic valve repair. METHODS: A retrospective chart review of all patients aged less than 18 years who underwent aortic valve repair from May 1985 to April 2020 was conducted. Mortality was cross-checked with the national health insurance database (96% complete mortality follow-up in April 2020). Primary study endpoints were survival and incidence of reoperations. RESULTS: From May 1985 until April 2020, 126 patients underwent aortic valve repair at a median age of 1.8 years (interquartile range, 0.2-10). Early mortality was 5.6% (7 of 126). All early deaths occurred in neonates with critical aortic stenosis undergoing commissurotomy. No early deaths were observed after 2002. Kaplan-Meier estimated survival was 90.8% (95% CI, 84.0-94.8) at 10 years, 86.9% (95% CI, 78.7-92.2) at 20 years, and 83.5% (95% CI, 71.7-90.6) at 30 years. The cumulative incidence of aortic valve replacement was 37% (95% CI, 27.7-46.3) at 10 years, 62.2% (95% CI, 50.1-72.1) at 20 years, and 67.4% (51.2-79.2) at 30 years. Nine patients had undergone re-repair of the aortic valve. The majority of valve replacements were Ross procedures. CONCLUSIONS: Our results support a repair-first strategy for patients with congenital heart disease and underline that aortic valve reconstruction can be a successful long-term solution. Longevity did not differ between aortic valve commissurotomy and complex aortic valve reconstruction.


Asunto(s)
Estenosis de la Válvula Aórtica , Procedimientos Quirúrgicos Cardíacos , Implantación de Prótesis de Válvulas Cardíacas , Recién Nacido , Niño , Humanos , Lactante , Adolescente , Válvula Aórtica/cirugía , Estudios Retrospectivos , Estudios de Seguimiento , Procedimientos Quirúrgicos Cardíacos/métodos , Estenosis de la Válvula Aórtica/cirugía , Reoperación , Resultado del Tratamiento , Implantación de Prótesis de Válvulas Cardíacas/métodos
13.
Dermatol Pract Concept ; 12(4): e2022197, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36534530

RESUMEN

Introduction: Early diagnosis can improve melanoma prognosis. Dermoscopy can enhance early melanoma recognition. Objectives: Examine the dermoscopy features of early melanoma up to a maximum surface diameter of 6 mm. Methods: Consecutive melanoma cases were collected from two medical practices in Sydney, Australia 2019-2021. Dermoscopy features were recorded for melanomas by maximum surface diameter, to the nearest 0.1 mm, to a limit of 6 mm. Results: Total cases numbered 100; with males (N = 48) and females (N = 52), melanoma in situ (MIS, N = 96) and invasive (N = 4). The most frequent anatomic sites on both males and females were back (males N = 20, females N = 16) then knee or leg (males N = 8, females N = 12). Minimum respective MIS diameters for males/females was 1.2/2.0 mm and for invasive cases 2.0/3.4 mm. Highest frequency dermoscopy features were: light brown, dark brown, gray and asymmetric melanoma shape. Brown pigment in hair follicles were more frequent on legs compared to other anatomic sites (odds ratio [OR] 14.6; 95% CI 1.29-165.17, P 0.03). Pseudopods were substantially increased in frequency comparing diameters less than 4 mm with 4 up to 6 mm (OR 8.81; 95% CI 1.05-73.9, P 0.004). Structureless area cases recorded increased gray (OR 7.08; 95% CI 1.61-31.11, P=0.01). Melanomas with edge angulation were noted in 20%-50% of cases across diameters 1-6 mm, less frequent were pigmented circles and polygons. Conclusions: Watch out! MIS presented with a surface diameter of just 1.2 mm and invasive melanoma 2.5 mm. Pseudopods were a strong clue to melanomas with a surface diameter less than 5mm. We found melanomas on leg sites displayed more frequent pigmented hair follicles.

14.
BMC Urol ; 22(1): 184, 2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36380340

RESUMEN

BACKGROUND: Despite the generally accepted World Health Organization guidelines on semen analysis, an individual's results can display significant variation when performed across time or in different laboratories. Semen parameters are in fact highly variable measures that can differ significantly between various analyses. Numerous researchers have discovered a wide range of semen parameters within each individual male, but only a few studies included the analysis of semen parameters variability in patients with infertility. The aim of this study was to evaluate the inter- and intra-individual variability of semen parameters in men of reproductive age with normozoospermia and those with oligozoospermia. METHODS: Five hundred and thirteen who provided ≥ 2 semen samples (798 samples in total) using an at-home mail-in kit over a period of about 2 years were enrolled in the study. Semen samples collection using Give Legacy at-home mail-in semen collection kit; semen analysis at a CLIA-certified laboratory. RESULTS: The degree of intra-subject variation across all semen parameters was lower in men with normozoospermia compared to men with oligozoospermia. Men with normozoospermia furthermore demonstrated a level of intra-subject variation that was lower than inter-subject variation across all measured parameters. No association was observed between intra-subject coefficients of variation in any of the semen parameters, including sperm concentration, sperm count, motile sperm count, total motility, progressive motility, the percentage of sperm with normal morphology, and the age, duration of abstinence, and BMI of the men. CONCLUSION: The results of this observational study confirm the significant variability in semen parameters in men with normozoospermia and oligozoospermia, as measured from at-home semen collection kit samples. This further underscore the importance of securing multiple samples for analysis to provide a robust assessment of male fertility.


Asunto(s)
Infertilidad Masculina , Oligospermia , Masculino , Humanos , Semen , Motilidad Espermática , Oligospermia/diagnóstico , Recuento de Espermatozoides , Espermatozoides , Infertilidad Masculina/diagnóstico
15.
J Clin Med ; 11(16)2022 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-36013142

RESUMEN

(1) Introduction: In the present study, we investigate the prognostic value of platelet-to-lymphocyte ratio (PLR) as a marker of severity and mortality in COVID-19 infection. (2) Methods: Between 1 March and 30 April 2020, we conducted a multicenter, retrospective cohort study of patients with moderate to severe coronavirus 19 (COVID-19), all of whom were hospitalized after being admitted to the emergency department (ED). (3) Results: A total of 1035 patients were included in our study. Neither lymphocytes, platelets or PLR were associated with disease severity. Lymphocyte count was significantly lower and PLR values were significantly higher in the group of patients who died, and both were associated with mortality in the univariate analysis (OR: 0.524, 95% CI: (0.336−0.815), p = 0.004) and (OR: 1.001, 95% CI: (1.000−1.001), p = 0.042), respectively. However, the only biological parameter significantly associated with mortality in the multivariate analysis was platelet count (OR: 0.996, 95% CI: (0.996−1.000), p = 0.027). The best PLR value for predicting mortality in COVID-19 was 356.6 (OR: 3.793, 95% CI: (1.946−7.394), p < 0.001). (4) Conclusion: A high PLR value is however associated with excess mortality.

16.
Ophthalmologica ; 245(5): 421-430, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35878587

RESUMEN

INTRODUCTION: The transition from a normal fundus to one with early drusen (≥20 small hard drusen) to age-related macular degeneration (AMD) in the form of drusen ≥63 µm in diameter is of interest, because small hard drusen may be precursors of large drusen. Study of AMD precursor lesions may provide valuable insight into factors that initiate AMD. Here, the progression of drusen was studied over an interval of 20 years in a population-based twin cohort. METHODS: Single-center, 20-year follow-up of 138 twins include biometry, fundus optical coherence tomography, and fundus photography. Macular characteristics were hierarchically classified as (per eye) (1) <20 small hard drusen, (2) ≥20 small hard drusen, (3) drusen ≥63 µm, or (4) ≥20 small hard drusen combined with drusen ≥63 µm. Additive and dominant genetic effects as well as shared and nonshared environmental effects were analyzed in a bivariate biprobit model with a classic liability-threshold approach and polygenic modeling with random effects. RESULTS: Median participant age was 59 (range 41-66) years. Of 25 (18%) cases of incident macular drusen, 7 had ≥20 small hard drusen, and 18 had drusen ≥63 µm at follow-up, whereas no participant had developed both traits simultaneously. Smoking was associated with incident ≥20 small hard drusen (p = 0.04) and incident drusen ≥63 µm (p = 0.003). Having ≥20 small hard drusen at baseline was associated with incident drusen ≥63 µm at follow-up (p = 0.02). Development of drusen ≥63 µm was attributable to 49% genetic effects and 51% environmental effects. CONCLUSION: The risk of progressing from 0 to 19 small hard macular drusen per eye to having ≥20 small hard drusen or drusen ≥63 µm at follow-up was associated with smoking and genetic predisposition. Having ≥20 small hard drusen in the absence of drusen ≥63 µm at baseline was associated with incident drusen ≥63 µm when examined 20 years later. The study confirms that small hard macular drusen is a forewarning of AMD and that progression to AMD may be hindered by avoidance of smoking.


Asunto(s)
Degeneración Macular , Drusas Retinianas , Adulto , Anciano , Humanos , Persona de Mediana Edad , Estudios de Cohortes , Estudios de Seguimiento , Degeneración Macular/complicaciones , Drusas Retinianas/diagnóstico , Drusas Retinianas/epidemiología , Drusas Retinianas/etiología , Factores de Riesgo , Tomografía de Coherencia Óptica
17.
J Immunother Cancer ; 10(5)2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35550554

RESUMEN

BACKGROUND: Vaginal melanoma (VM) is a rare cancer and has a poor response to immune checkpoint blockade (ICB). CD8+Tissue Resident Memory (TRM) T cells proliferate in response to ICB and correlate with longer survival in metastatic cutaneous melanoma. However, their capacity to respond to VM and their neoantigens is not known. METHODS: Using longitudinal samples, we explored the evolution of VM mutations by whole-exome sequencing and RNAseq, we also defined the immune context using multiplex immunohistochemistry and nanostring pan cancer immune profile. Then using fresh single cell suspensions of the metastatic samples, we explored VM T cells via mass cytometry and single cell RNAseq and T cell receptor sequencing (TCRseq). Finally, we investigated TRM, pre-TRM and exhausted T cell function against melanoma neo-antigens and melanoma differentiation antigens in vitro. RESULTS: Primary VM was non-inflamed and devoid of CD8+ TRM cells. In contrast, both metastases showed proliferating CD8+ TRM were clustered at the tumor margin, with increased numbers in the second ICB-refractory metastasis. The first metastasis showed dense infiltration of CD8+ T cells, the second showed immune exclusion with loss of melanoma cell Major histocompatibility complex (MHC)-I expression associated with downregulation of antigen presentation pathway gene expression. CD8+ TRM from both metastases responded to autologous melanoma cells more robustly than all other CD8+ T cell subsets. In addition, CD8+ TRM shared TCR clones across metastases, suggesting a response to common antigens, which was supported by recognition of the same neoantigen by expanded tumor infiltrating lymphocytes. CONCLUSIONS: In this study, we identified TRM clusters in VM metastases from a patient, but not primary disease. We showed TRM location at the tumor margin, and their superior functional response to autologous tumor cells, predicted neoantigens and melanoma differentiation antigens. These CD8+ TRM exhibited the highest tumor-responsive potential and shared their TCR with tumor-infiltrating effector memory T cells. This suggests VM metastases from this patient retain strong antitumor T cell functional responses; however, this response is suppressed in vivo. The loss of VG MHC-I expression is a common immune escape mechanism which was not addressed by anti-PD-1 monotherapy; rather an additional targeted approach to upregulate MHC-I expression is required.


Asunto(s)
Melanoma , Neoplasias Cutáneas , Linfocitos T CD8-positivos , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico , Memoria Inmunológica , Células T de Memoria , Neoplasias Cutáneas/metabolismo
18.
J Patient Rep Outcomes ; 6(1): 30, 2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-35362836

RESUMEN

INTRODUCTION: The current service metrics used to evaluate quality in emergency care do not account for specific healthcare outcome goals for older people living with frailty. These have previously been classified under themes of 'Autonomy' and 'Functioning'. There is no person-reported outcome measure (PROM) for older people with frailty and emergency care needs. This study aimed to identify and co-produce recommendations for instruments potentially suitable for use in this population. METHODS: In this systematic review, we searched six databases for PROMs used between 2010 and 2021 by older people living with frailty receiving acute hospital care. Studies were reviewed against predefined eligibility criteria and appraised for quality using the COSMIN Risk of Bias checklist. Data were extracted to map instrument constructs against an existing framework of acute healthcare outcome goals. Instrument face and content validity were assessed by lay collaborators. Recommendations for instruments with potential emergency care suitability were formed through co-production. RESULTS: Of 9392 unique citations screened, we appraised the full texts of 158 studies. Nine studies were identified, evaluating nine PROMs. Quality of included studies ranged from 'doubtful' to 'very good'. Most instruments had strong evidence for measurement properties. PROMs mainly assessed 'Functioning' constructs, with limited coverage of 'Autonomy'. Five instruments were considered too burdensome for the emergency care setting or too specific for older people living with frailty. CONCLUSIONS: Four PROMs were recommended as potentially suitable for further validation with older people with frailty and emergency care needs: COOP/WONCA charts, EuroQol, McGill Quality of Life (Expanded), and Palliative care Outcome Scale.

19.
Dalton Trans ; 51(12): 4734-4748, 2022 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-35244111

RESUMEN

Polymorphism is observed in the Y3+xRh4Ge13-x series. The decrease of Y-content leads to the transformation of the primitive cubic Y3.6Rh4Ge12.4 [x = 0.6, space group Pm3̄n, a = 8.96095(9) Å], revealing a strongly disordered structure of the Yb3Rh4Sn13 Remeika prototype, into a body-centred cubic structure [La3Rh4Sn13 structure type, space group I4132, a = 17.90876(6) Å] for x = 0.4 and further into a tetragonal arrangement (Lu3Ir4Ge13 structure type, space group I41/amd, a = 17.86453(4) Å, a = 17.91076(6) Å) for the stoichiometric (i.e. x = 0) Y3Rh4Ge13. Analogous symmetry lowering is found within the Y3+xIr4Ge13-x series, where the compound with Y-content x = 0.6 is crystallizing with La3Rh4Sn13 structure type [a = 17.90833(8) Å] and the stoichiometric Y3Ir4Ge13 is isostructural with the Rh-analogue [a = 17.89411(9) Å, a = 17.9353(1) Å]. The structural relationships of these derivatives of the Remeika prototype are discussed. Compounds from the Y3+xRh4Ge13-x series are found to be weakly-coupled BCS-like superconductors with Tc = 1.25, 0.43 and 0.6, for x = 0.6, 0.4 and 0, respectively. They also reveal low thermal conductivity (<1.5 W K-1 m-1 in the temperature range 1.8-350 K) and small Seebeck coefficients. The latter are common for metallic systems. Y3Rh4Ge13 undergoes a first-order phase transition at Tf = 177 K, with signatures compatible to a charge density wave scenario. The electronic structure calculations confirm the instability of the idealized Yb3Rh4Sn13-like structural arrangements for Y3Rh4Ge13 and Y3Ir4Ge13.

20.
Acta Ophthalmol ; 100(8): e1561-e1568, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35322936

RESUMEN

PURPOSE: To study age- and sex-adjusted heritability of small hard drusen and early age-related macular degeneration (AMD) in a population-based twin cohort. METHODS: This was a single-centre, cross-sectional, classical twin study with ophthalmic examination including refraction, biometry, best-corrected visual acuity assessment, colour and autofluorescence fundus photography, and fundus optical coherence tomography. Grading and categorization of drusen was by diameter and location. RESULTS: The study enrolled 176 same-sex pairs of twins of mean (SD) age 58.6 (9.9) years. The prevalence of the four phenotypes ≥20 small hard macular drusen (largest diameter < 63 µm), ≥20 small hard extramacular drusen, intermediate drusen (63-125 µm) anywhere, and large drusen (>125 µm) anywhere was 12.4%, 36.4%, 5.8%, and 8.4%, respectively, and the respective heritabilities, adjusted for age and sex, were 78.2% [73.5-82.9], 69.1% [62.3-75.9], 30.1% [4.1-56.1], and 65.6% [26.4-100]. Age trajectory analysis supported a gradual transition to larger numbers of small hard drusen with increasing age. The heritability of ≥20 small hard drusen was markedly lower than the 99% found in the 40% overlapping twin cohort that was seen 20 years earlier. CONCLUSION: Numerous (≥20) small hard drusen and larger drusen that fit the definition of dry AMD were highly heritable. Small hard drusen counts increased with age. Decreasing heritability with increasing age suggests that the impact of behavioural and environmental factors on the development of small hard drusen increases with age.


Asunto(s)
Atrofia Geográfica , Degeneración Macular , Drusas Retinianas , Humanos , Drusas Retinianas/diagnóstico , Drusas Retinianas/epidemiología , Drusas Retinianas/genética , Estudios Transversales , Degeneración Macular/diagnóstico , Degeneración Macular/epidemiología , Degeneración Macular/genética , Gemelos Monocigóticos , Tomografía de Coherencia Óptica
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